Penfigoide ampollar por teneligliptina / Teneligliptin-induced bullous pemphigoid

El Penfigoide Ampollar por fármacos es una variedad de penfigoide ampollar en la que un medicamento actúa como causa o desencadenante de la enfermedad. Clínicamente se manifiesta como ampollas tensas de contenido seroso localizadas fundamentalmente en abdomen, miembros superiores y raíz de muslos. El estudio histopatológico evidencia ampollas subepidérmicas e infiltrado dérmico mixto con eosinófilos. La inmunofluorescencia directa de piel sana perilesional muestra depósitos lineales de IgG y/o C3. Sin embargo, en hasta 15% de los casos puede ser negativa. Los pacientes diabéticos que reciben tratamiento con fármacos del grupo de los inhibidores de la dipeptidilpeptidasa 4, también conocidos como gliptinas, tienen 3 veces más riesgo de desarrollar esta patología. El tiempo de latencia entre el inicio de la medicación y la aparición de los síntomas es variable, con una media de 10 meses. El tratamiento radica en la suspensión inmediata del fármaco causal y la administración de prednisona oral 0,5 mg/kg/día. El tiempo medio de respuesta es de 10 días. Se presenta un varón de 82 años con una dermatosis ampollar pruriginosa de 3 semanas de evolución posterior al inicio de teneligliptina, cuyo estudio histopatológico fue característico de penfigoide ampollar, y que evolucionó satisfactoriamente al suspender el hipoglucemiante oral, sin aparición de nuevas lesiones a más de un año de seguimiento clínico

Drug-induced bullous pemphigoid is a variety of bullous pemphigoid in which a drug is the cause of the disease. It manifests as serous tense blisters located mainly on the abdomen, upper limbs and root of the tights. The histopathology shows subepidermal bullae and mixed dermal infiltrate with eosinophils. Direct immunofluorescence of healthy perilesional skin shows linear IgG and/or C3 deposits. However, it can be negative in up to 15% of the cases. Diabetic patients receiving dipeptidylpeptidase 4 inhibitors have a 3 times increased risk of developing drug-induced bullous pemphigoid. The mean time between the beginning of the medication and the appearance of the dermatosis is 10 months. Immediate suspension of the offending drug and administration of prednisone 0,5 mg/kg/day is the standard treatment. Average response time is 10 days. We present an 82-year-old-man with a 3-week itchy bullous dermatosis that started 8 months after treatment with teneligliptin, whose histopathological study resembled bullous pemphigoid, and which evolved satisfactorily when the drug was discontinued. No new lesions have been detected after more than one year of clinical follow-up. Key words: bullous pemphigoid, drug-induced bullous pemphigoid, gliptins, teneligliptin, dipeptidylpeptidase 4 inhibitors

A case report of cutaneous plasmacytosis / 北京大学学报(医学版)

A collection of plasma cells in the skin can represent a broad spectrum of disease entities. Secondary syphilis, primary cutaneous plasmacytoma, primary cutaneous plasmacytosis, cutaneous lymphoid hyperplasia and nodular amyloidosis are considered possible differential diagnoses. The primary cutaneous plasma cell disorders can range from malignant to benign plasma cell neoplasms. The malignant conditions are neoplastic diseases having monoclonal proliferations, rapid progression and fatal outcome while the benign plasma cell disorders usually show polyclonality, chronicity and benign process, including plasmacytosis. We present a case of cutaneous plasmacytosis. The patient was a 34-year-old man, presented with disseminated reddish-brown plaques and nodules on the right side of the hips, inguinal groove, and the thigh. Histopathologically, mature plasma cells perivascular infiltrates were observed mainly in the dermis. Polyclonality of infiltrating plasma cells with coexistence of both kappa and gamma chain-positive cells demonstrated with immunohistochemistry, as well as CD20+++, CD38++++, CD79a++++, CD138++, Ki67<30%. The diagnosis, cutaneous plasmacytosis, was established by the pertinent laboratory findings. Primary cutaneous plasmacytosis was an uncommon reactive lymphoplasmacytic disorder of uncertain etiology. Cutaneous plasmacytosis is a rare disease characterized by peculiar multiple eruptions and hyper gamma globulinemia. It has been mainly described in patients of Japanese descent, with only few reports in Caucasians and Chinese, although information concerning the disorder was limited to individual case reports. Cutaneous plasmacytosis is a rare disorder, which is characterized by multiple red to dark-brown nodules and plaques on the trunk and usually associated with polyclonal hyper gamma globulinaemia. Primary cutaneous plasmacytosis or cutaneous plasmacytosis was thought to be a reactive process with unknown etiology. Histologically, lesions contain dense perivascular infiltration of mature polyclonal plasma cells without any atypia, in the dermis and subcutaneous fat. The clinical course is chronic and benign without spontaneous remission. Available treatments for cutaneous plasmacytosis include psoralen ultraviolet A radiotherapy, systemic chemotherapy and intralesional steroid injection. The patient with cutaneous plasmacytosis in this report was treated with tacrolimus ointment and psoralen ultraviolet A.

Inmunopatogenia de la psoriasis: nuevos avances / Inmunopatogenia of psoriasis. New progress

La psoriasis es una enfermedad inflamatoria crónica de la piel. Su etiología es multifactorial e incluye susceptibilidad genética, factores inmunológicos y múltiples elementos ambientales, que pueden desencadenar y/o exacerbar la enfermedad. En las últimas décadas se han realizado investigaciones minuciosas sobre la patogénesis de la psoriasis, han sido reconocidos varios subtipos de células T que tienen un papel fundamental en el establecimiento de la inflamación en lesiones cutáneas. Los estudios genéticos brindan las bases para la construcción del modelo de la enfermedad, demostrando que las células dendríticas, los linfocitos T y los queratinocitos desempeñan un rol clave en la patología de esta entidad, así como también un conjunto de citoquinas que impulsan la inflamación psoriásica, dentro de las que se incluyen TNFα, IL-22, IL-23 e IL-17, las cuales promueven la respuesta inflamatoria de queratinocitos, y la producción de péptidos antimicrobianos, citoquinas y quimiocinas, perpetuando así la respuesta inflamatoria. En la actualidad, el desarrollo de varios fármacos biológicos altamente eficaces ha revolucionado el tratamiento de la psoriasis en placas de moderada a severa. Estos medicamentos son un reflejo de una mayor comprensión de la patogénesis de la psoriasis, incluyendo la importancia central de IL-23 e IL17 y las diferentes vías de señalización. El objetivo de este trabajo es realizar una revisión crítica de la literatura sobre la psoriasis y los mecanismos implicados en su imnunopatogenia(AU)

Psoriasis is a chronic inflammatory disease of the skin. Its etiology involves several agents such as genetic susceptibility, immunological factors and multiple environmental elements, which can trigger and / or exacerbate the disease. In recent decades thorough research has been conducted on the pathogenesis of psoriasis, several T-cell subtypes that play a key role in the establishment of inflammation in skin lesions have been recognized. Genetic studies provide the basis for the construction of the disease model, demonstrating that dendritic cells, T lymphocytes and keratinocytes play a key role in the pathology of this entity, as well as a set of cytokines that drive psoriatic inflammation , such as include TNF , IL-22, IL-23 and IL-17, which promote the inflammatory response of keratinocytes, and the production of antimicrobial peptides, cytokines and chemokines, thus perpetuating the inflammatory response. At present, the development of several highly effective biological drugs has revolutionized the treatment of moderate to severe plaque psoriasis. These drugs are a reflection of a greater understanding of the pathogenesis of psoriasis, including the central importance of IL-23 and IL-17 and different signaling pathways. The objective of this work is to perform a critical review of the literature on psoriasis and the mechanisms involved in its imnunopathogenesi(AU)

Skin disorders in renal transplant recipients: a retrospective study

Abstract: Background: Immunosuppressive therapy, which is necessary to avoid graft rejection in renal transplant recipients, presents an increased risk of several pathologies, namely infectious and neoplastic. Objectives: To identify the most frequent skin diseases and their clinical and demographical risk factors within a population of renal transplant recipients. Methods: A retrospective study of renal transplant recipients referred to dermatology visit and observed for the first time from January 2008 to December 2014. Results: The study included 197 patients, 120 men (60,9%). Mean age was 50,7 years (±13,4). 12 patients (6,1%) had previous skin cancer. Infections were the most frequent reason of referral (93/197; 44%). From the total referred, 18,3% (36/197) presented pre-cancerous lesions. Malignancy was diagnosed in 36 patients (18,3%), with 29 non-melanoma skin cancers (14,7%) and 7 Kaposi sarcomas (3,6%). Ratio of basal cell carcinoma to squamous cell carcinoma was 1,1:1. Non-melanoma skin cancer was significantly associated with older age (p = 0,002), male gender (p = 0,028), history of previous skin cancer (p = 0,002) and higher duration of immunosuppressive therapy (p<0,001). Study limitations: Retrospective study, with data from the first visit in dermatology. We didn't made classification on skin-types. Conclusions: The great incidence of cutaneous infections and skin cancer is responsible for a significant morbidity. It is important to assure the regular dermatological follow-up of renal transplant recipients, which will promote the prevention, an early diagnosis and an efficient treatment.

Skin symptoms as diagnostic clue for autoinflammatory diseases

ABSTRACT Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis.

Inflammasomes and dermatology

Abstract: Inflammasomes are intracellular multiprotein complexes that comprise part of the innate immune response. Since their definition, inflammasome disorders have been linked to an increasing number of diseases. Autoinflammatory diseases refer to disorders in which local factors lead to the activation of innate immune cells, causing tissue damage when in the absence of autoantigens and autoantibodies. Skin symptoms include the main features of monogenic inflammasomopathies, such as Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA). Concepts from other pathologies have also been reviewed in recent years, such as psoriasis, after the recognition of a combined contribution of innate and adaptive immunity in its pathogenesis. Inflammasomes are also involved in the response to various infections, malignancies, such as melanoma, autoimmune diseases, including vitiligo and lupus erythematosus, atopic and contact dermatitis, acne, hidradenitis suppurativa, among others. Inhibition of the inflammasome pathway may be a target for future therapies, as already occurs in the handling of CAPS, through the introduction of IL-1 inhibitors. This study presents a literature review focusing on the participation of inflammasomes in skin diseases.

Manifestaciones mucocutáneas del paciente pediátrico con enfermedades autoinmunes del Hospital Roberto del Río / Mucocutaneous manifestations of the pediatric patient with autoimmune diseases of the Roberto del Río Hospital

Las enfermedades autoinmunes son desórdenes heterogéneos que pueden comprometer distintos órganos. Su frecuencia es baja, se estima que 3 de cada 1.000 niños cursan con alguna condición reumatológica. Las patologías reumatológicas más comunes en la edad pediátrica son la artritis idiopática juvenil (AIJ) seguida por el lupus eritematoso sistémico (LES), dermatomiositis juvenil (DMJ), vasculitis primarias y la esclerodermia. Materiales y Métodos: Se efectuó un estudio descriptivo retrospectivo de pacientes pediátricos atendidos en el servicio de inmunología del Hospital Roberto del Rio entre los años 1990 y 2011. Se pesquisaron un total de 102 pacientes, con diagnósticos de AIJ, LES y DMJ. Se diseñó una ficha de protocolo, con los datos: edad, sexo, antecedentes familiares, manifestaciones cutáneas al diagnóstico y a lo largo de la evolución. Para el análisis estadístico de variables, se utilizó el programa STATA 8.0. Resultados: El 45,45% de los pacientes con AIJ presentó lesiones cutáneas, sin embargo, sólo un 20% de ellas, relacionadas a esta enfermedad. El 91,7% de los pacientes con LES presentó manifestaciones cutáneas, siendo la vasculitis cutánea y el eritema malar, las más frecuentes. En los pacientes con DMJ, el eritema heliotropo y pápulas de Gottron fueron las manifestaciones cutáneas más comunes. Conclusión: Los hallazgos cutáneos cobran un rol muy importante en el diagnostico enfermedades autoinmunes. Estos datos demuestran la importancia de un examen dermatólogico exhaustivo para su diagnóstico precoz y evitar sus complicaciones.

Background: Autoimmune diseases are disorders that can compromise different organs. Its frequency is low, it is estimated that 3 out of every 1,000 children are affected with any rheumatologic condition. The most common rheumatic diseases in children are juvenile idiopathic arthritis (JIA) followed by systemic lupus erythematosus (SLE), juvenile dermatomyositis (DMJ), primary vasculitis and esclerodermia.2 Materials and Methods: A retrospective study was conducted in pediatric patients seen in the Department of Immunology from the Roberto del Rio Hospital between 1990 and 2011. Records of 105 patients with the diagnosis of juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM) have been included. We designed a protocol file with the given data: Age, sex, family history, skin manifestations at the diagnosis and throughout the evolution. The program STATA 8.0 was used for statistical analysis of variable. Results: 45.45% of JIA patients had some type of skin lesions, however, only 20% of them related to this disease. 91.7% of SLE patients presented cutaneous manifestations, the most common being cutaneous vasculitis and malar erythema. In patients with JDM, heliotrope erythema and papules Gottron were the most common skin manifestations. Discussion: Cutaneous manifestations have a very important role in autoimmune diseases. While the diagnosis and management of these diseases require a multidisciplinary team, these data demonstrate the importance of an exhaustive physical examination for early diagnosis and thereby reduce complications. Conclusions: This study highlights the importance of the dermatologist in an early diagnosis of rheumatic diseases.

Syndrome in Question

Immunoglobulin light chain amyloidosis is the most common acquired systemic amyloidosis. Its presentation is often insidious and progressive, which may delay diagnosis. The authors describe a rare case of immunoglobulin light chain amyloidosis in a 34-year-old man with scleroderma-like manifestation substantiated by multifarious laboratory investigations and the histopathologic feature of involved skin lesions stained with Congo red and crystal violet. This helps to maintain a high clinical suspicion of the disease when confronting similar skin presentation.

IgG/IgA pemphigus reactive with desmoglein 1 with additional undetermined reactivity with epidermal basement membrane zone.

IgG/IgA pemphigus is an extremely rare subset of pemphigus, showing anti-keratinocyte cell surface antibodies of both IgG and IgA classes. Herein, we describe a unique case of IgG/IgA pemphigus with clinical features of edematous erythema and peripheral vesiculopustules. Histopathology showed the presence of subcorneal pustules and acantholytic blisters in the mid-epidermis with neutrophilic infiltration and eosinophilic spongiosis. Direct immunofluorescence of perilesional skin showed both IgG and IgA deposits to keratinocyte cell surfaces and unusual granular deposits of IgG, IgM, and C3 along basement membrane zone. On enzyme linked immunosorbent assay , the auto-antibodies were found to be reactive to desmoglein 1 antigen. Various clinical, histopathological, and immunological findings in our case overlapped with the features of IgA pemphigus, pemphigus herpetiformis, and pemphigus foliaceus. These findings indicate that IgG/IgA pemphigus may be a transitional form between IgA pemphigus and pemphigus herpetiformis, and thus provides insight into the pathogenicity of this rare disorder.

Disseminated histoplasmosis: A comparative study of the clinical features and outcome among immunocompromised and immunocompetent patients.

Background. Disseminated histoplasmosis is a chronic granulomatous disease caused by the dimorphic fungus, Histoplasma capsulatum. Clinical presentation can vary from the acute pulmonary to the chronic disseminated form. In India, disseminated histoplasmosis often presents with pyrexia of unknown origin with a presentation similar to ‘disseminated tuberculosis’ involving the adrenal glands and bone marrow. Due to rarity of the disease, data are lacking regarding its clinical presentation and outcome among immunocompromised and immunocompetent patients. Methods. During January 2000 to December 2010, we identified 37 patients of disseminated histoplasmosis and attempted to characterize the differences between immunocompromised and immunocompetent patients. Demographic characteristics, clinical presentation, risk factors, laboratory findings, diagnostic yield, treatment received and prognosis were noted and compared between the two groups. Results. Eleven of 37 patients with disseminated histoplasmosis were immunocompromised and 26 were immunocompetent. Comparison of their clinical features showed a higher frequency of skin lesions in the immunocompromised compared to the immunocompetent group (54.5% v. 11.5%). Pancytopenia and anaemia were more common among the immunocompromised (81.8%) compared to the immunocompetent (46.2%) group. In the immunocompromised patients, the diagnosis was made most often by bone marrow aspirate and culture (72.7%) compared to the immunocompromised group where the diagnosis was most often obtained by adrenal gland biopsy and fungal cultures (57.7%). The cure rate was significantly higher in the immunocompetent group (73% v. 45%). Conclusion. The clinical presentation and outcome of patients with disseminated histoplasmosis differs among immunocompromised and immunocompetent patients.

Virus Papiloma Humano (HPV): Parte II - Clínica y terapéutica / Human Papilloma Virus (HPV). Part II – Clinic and therapeutics

Los virus papiloma humano (HPV) pertenecen a la familia de los Papovaviridae y están ampliamente distribuidos en la naturaleza. Se han identificado más de 130 tipos. Pueden comprometer la piel y mucosas provocando lesiones benignas llamadas verrugas. Algunos tipos se asocian con el desarrollo de procesos malignos epiteliales. La respuesta inmune del huésped cumple un rol importante en el control de la infección. El diagnóstico es esencialmente clínico, pero a veces se recurre al estudio histopatológico de las lesiones o al empleo de técnicas de biología molecular. Existe una variedad de opciones terapéuticas, la mayoría destinada a destruir las lesiones. Últimamente se han desarrollado vacunas preventivas para algunos tipos de HPV y se encuentran en experimentación las vacunas terapéuticas.

The human papillomavirus belongs to the family of the Papillomaviridae. This virus is widely distributed in the nature. More than 130 types have been indentifi ed; they can compromise the skin and mucous membranes provoking benign injuries called warts. Some types of virus are said to be involved in the development of precancerous skin lesions. The host immune response has an important role on controlling the infection. The diagnosis is essentially clinic, nevertheless, sometimes histopathologic study of lesions or molecular biology techniques are needed in order to reach an accurate diagnosis. There is a great variety of treatment options; most of them aim to destroy the lesion. Lately some vaccines have been being developed; these are only for some types of HPV and are still under experimental designs (Dermatol Argent 2010;16(2):102-109).

Lepra histioide de Wade / Hystioid leprosy of Wade

En el presente artículo se expondrá un caso de lepra histioide de Wade, una forma clínico-histopatológica especial de lepra multibacilar caracterizada por la presencia de lesiones papulosas o nodulares correspondientes a lepromas conformados por histiocitos de morfología fusiforme. Se examinarán las características principales de esta forma particular de expresión de la lepra, sus diferencias con la forma clásica de presentación y los diagnósticos diferenciales que deben considerarse.

Linfoma anaplásico de células grandes CD30+ con manifestaciones cutáneas: a propósito de un caso y revisión de la literatura / CD30+ anaplastic large cell lymphoma with cutaneous manifestations: case report and literature review

Los linfomas CD30+ de la piel representan un grupo heterogéneo de neoplasias con morfología, inmunofenotipo y clínica variables: en un extremo del espectro se encuentra la papulosis linfomatoide, de curso generalmente indolente, y en el otro extremo, el agresivo linfoma anaplásico de células grandes CD30+ (ALCL) sistémico. Presentamos una paciente de sexo femenino de 48 años de edad, con diagnóstico de ALCL con mala evolución. Analizaremos a continuación aspectos fundamentales del diagnóstico y tratamiento de esta patología.

Clinical profile of Chikungunya in infants.

OBJECTIVE: To define the clinical manifestations of Chikungunya infection in infants. METHODS: The inclusion criteria was fever (defined as axillary temperature > 99.6 degrees F) with any one of the following features; seizure, loose stools, peripheral cyanosis, skin manifestations or pedal edema in children less than one year. Details of disease from onset of illness till admission were noted and a thorough clinical examination was done at the time of admission. Daily follow-up was performed and the serial order of appearance of clinical features was noted till complete recovery. The sera collected from patients after the 7th day of onset of fever was analyzed for specific chikungunya antibody by IgM antibody capture enzyme linked immunosorbent assay (ELISA). RESULTS: Fifty six (56) infants were laboratory confirmed for chikungunya, consisting of 34 (60.71%) males and 22 (39.29%) females. 4 (7.14%) infants were less than 1 month of age, 39 (69.64%) 2-6 months old and 13 (23.21%) 7-12 months old. Fever was invariably present, but associated constitutional symptoms in infants consisted of lethargy or irritability and excessive cry. The most characteristic feature of the infection in infants was acrocyanosis and symmetrical superficial vesicobullous lesions were noted in most infants. Erythematous asymmetrical macules and patches were observed which later progressed to morbiliform rashes. The face and oral cavity was spared in all observed patients. CONCLUSION: An entirely different spectrum of disease is seen in infants with chikungunya as compared to older children who need to be carefully observed for. The morbidity and mortality of the disease may be avoided by the rational use of drugs and close monitoring of all infants.

Entendiendo la relación entre la infección por Helicobacter pylori y enfermedades alérgicas en niños y adultos / Understanding the relationship between Helicobacter pylori infection and allergies in children and adults

La infección por Helicobacter pylori afecta a más del 50 por ciento de la población mundial, asociándose a gastritis histológica, úlcera duodenal y gástrica, así como también a cáncer gástrico. Abundante literatura reciente sugiere una relación entre H. pylori y las enfermedades alérgicas, las cuales han presentado un sostenido aumento en su incidencia en los últimos años. Considerando que ambas enfermedades (H. pylori y alergias), presentan respuestas Th polarizadas y opuestas, se revisan los aspectos claves de esta infección y su respuesta inmune polarizada a Th1, la cual, siendo inefectiva para erradicar H. pylori, es el elemento característico subyacente de la gastritis crónica histológica. Junto con ésto se analiza la respuesta inmune de tipo Th2 sistémica asociada a alergias cutáneas, respiratorias y alimentarias, para así comprender mejor su posible interacción. Algunos estudios plantean que la erradicación de H. pylori beneficiaría la remisión de enfermedades tales como urticaria crónica,asma y alergias alimentarias entre otras. Por el contrario, una fuerte línea de investigación se apoyanen la teoría de higiene y plantean que la erradicaciónde microrganismos como H. pylori, Toxoplasma gondii y virus de hepatitis A aumentaría la incidencia de alergias por un desbalance hacia Th2. En la mayoría de los estudios, la falta de grupo control o protocolos ciegos dificultan la posibilidad de llegar a una conclusión.

Helicobacter pylori’s infection affects more than 50% of the world’s population, inducing a histologic chronic gastritis, which can develop to a duodenal and gastric ulceration, as well as gastric cancer. Recent literature suggests a possible relationship between H. pylori and allergic diseases, which have also shown an increase in their incidence these last years. Considering that both diseases, H. pylori and allergies, have polarized and opposite immune responses, we wanted to examine the important aspects of this infection and it’s immune response (Th1), which is ineffective in eradicating H. pylori, and is a characteristic element in the histologic chronic gastritis. We also wanted to review the immune response linked to skin, food and respiratory allergies (Th2) so we can understand the interaction between allergic diseases and H. pylori. Many of the studies conclude that the eradication of H. pylori would benefit the remission of chronic urticaria, asthma and food allergies among others. However, other studies mention the hygiene hypothesis where the eradication of microrganisms such as H. pylori, Toxoplasma gondii and hepatitis A virus could increase the incidence of allergic diseases due to a polarized response towards Th2. The lack of control groups and blind studies make difficult to establish a final conclusion

Enfermedad de injerto versus huésped / Graft-versus-host disease

La enfermedad de Injerto contra Huésped (EICH) es una cuadro que se produce en algunos de los pacientes receptores de un trasplante de médula ósea, en el cual los linfocitos T inmunocompetentes del tejido trasplantado reaccionan en contra de los tejidos del receptor (huésped). Se divide en dos grandes grupos: agudo y crónico. Sus manifestaciones clínicas son diversas, dadas por el compromiso variable de piel, hígado, tracto gastrointestinal, entre otros. Las lesiones cutáneas suelen ser el hallazgos más frecuente tanto en la forma aguda como crónica. Dada la existencia de múltiples procesos patológicos que pueden simular una EIDCH, su diagnóstico requiere, además de un alto índice de sospecha, el estudio histológico y el seguimiento cercano de los pacientes. Dado que cada vez son más frecuentes los trasplantes de médula ósea, así como sus manifestaciones más habituales y precoces ocurren en la piel, es muy importante para los dermatólogos estar familiarizados con este cuadro clínico.

Involvement of C4 allotypes in the pathogenesis of human diseases

O sistema complemento constitui um importante sistema de defesa humoral, exercendo papel relevante na resposta contra agentes microbianos, no controle da resposta inflamatória e na depuração de imunocomplexos. A ativação da via clássica é dependente da formação do complexo antígeno-anticorpo. O componente C4 do complemento participa da etapa inicial de ativação desta via e a sua expressão é determinada por dois alótipos : C4A e C4B. A deficiência dos alótipos de C4 tem sido relacionada a várias doenças. O objetivo do presente estudo foi avaliar os dados de literatura que descrevem as deficiências específicas de C4A e C4B com a finalidade de caracterizar seu significado clínico. Foi realizada uma ampla revisão bibliográfica através do MEDLINE e LILACS, avaliando-se os dados de literatura. Excluiu-se estudos com a avaliação de C4 total sem a análise dos alótipos e relatos de caso isolados de deficiência total de C4. Verificou-se que a deficiência dos alótipos de C4 está relacionada com algumas doenças: hanseníase, esclerose sistêmica com anticorpos anti-topoisomerase I, hiperplasia adrenal congênita intermediária com genótipo DR5, diabetes mellitus tipo 1 com genótipo DR3,4 e diabetes mellitus tipo 1 com anticorpos anti-células das ilhotas. Também foram observadas algumas associações entre C4B e doenças auto-imunes como lupus eritematoso sistêmico, ou que se supõe terem um componente autoûimune como o autismo. Estudos demonstraram associações do C4A com tireoidite pós-parto, esclerose limitada e esclerose sistêmica sem anticorpos anti-topoisomerase I. Porém, os estudos dos alótipos de C4 se concentraram em populações isoladas e alguns destes não conseguiram ser reproduzidos por outros autores.